Plasminogen Activator Inhibitor Type I Controls Cardiomyocyte Transforming Growth Factor-β and Cardiac Fibrosis

• Published in: Circulation (New York, N.Y.) Vol. 136; no. 7; pp. 664 - 679
• Main Authors: Flevaris, Panagiotis, Khan, Sadiya S., Eren, Mesut, Schuldt, Adam J. T., Shah, Sanjiv J., Lee, Daniel C., Gupta, Sweta, Shapiro, Amy D., Burridge, Paul W., Ghosh, Asish K., Vaughan, Douglas E.
• Format: Journal Article
• Language: English
• Published: United States by the American College of Cardiology Foundation and the American Heart Association, Inc 15.08.2017
• Subjects: Angiotensin II - pharmacology; Angiotensin II - therapeutic use; Animals; Bone Morphogenetic Protein 7 - pharmacology; Cardiomegaly - drug therapy; Cardiomegaly - metabolism; Cardiomegaly - pathology; Cells, Cultured; Female; Frameshift Mutation; Humans; Magnetic Resonance Imaging, Cine; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocytes, Cardiac - cytology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Plasminogen Activator Inhibitor 1 - deficiency; Plasminogen Activator Inhibitor 1 - genetics; Plasminogen Activator Inhibitor 1 - metabolism; RNA - chemistry; RNA - metabolism; Sequence Analysis, RNA; Smad6 Protein - antagonists & inhibitors; Smad6 Protein - genetics; Smad6 Protein - metabolism; Transcription, Genetic - drug effects; Transforming Growth Factor beta - metabolism; Transforming Growth Factor beta - pharmacology; cardiomyopathy; protease inhibitor; cardiac remodeling

BACKGROUND:Fibrosis is the pathological consequence of stress-induced tissue remodeling and matrix accumulation. Increased levels of plasminogen activator inhibitor type I (PAI-1) have been shown to promote fibrosis in multiple organ systems. Paradoxically, homozygous genetic deficiency of PAI-1 is...